Interleukin-3 treatment of rhesus monkeys leads to increased production of
histamine-releasing cells that express interleukin-3 receptors at high
levels
FC van Gils, ME van Teeffelen, KJ Neelis, J Hendrikx, H Burger, RW van Leen, E Knol, G Wagemaker and AW Wognum
Department of Hematology, Erasmus University, Rotterdam, The Netherlands.
To understand the hematopoietic and nonhematopoietic responses to
interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was
examined on bone marrow (BM) cells and peripheral blood (PB) cells of
rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R
expression is low in untreated monkeys, IL-3 administration led to a
gradual increase in both low- and high-affinity binding sites for IL-3.
This increase reflected the total number of cells expressing IL- 3Rs, as
detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+
cells in both BM and PB could be characterized as basophilic granulocytes
that contained high levels of histamine. In contrast to the effect on these
differentiated cells, IL-3 administration did not significantly alter the
low level IL-3R expression on immature, CD34+ cells. Further flow
cytometric analysis using biotinylated growth factors showed that the
IL-3R+ basophils also expressed receptors for granulocyte-macrophage
colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These
findings indicated that the IL-3R+ cells included neither monocytes, which
express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c-
kit. By combining flow cytometric and Scatchard data, it was calculated
that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs
and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3
treatment leads to the production of large numbers of cells that express
high levels of IL-3R and are capable of producing histamine provides an
explanation for the often severe allergic reactions that occur during
prolonged IL-3 administration. It also indicates that IL- 3, in addition to
its direct effects on hematopoietic cells, may also stimulate hematopoiesis
through the release of secondary mediators such as histamine by
IL-3-responsive mature cells.
Volume 86,
Issue 2,
pp. 592-597,
07/15/1995
Copyright © 1995 by The American Society of Hematology
